National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research, Huazhong Agricultural University, Wuhan, China.
Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China.
Nat Struct Mol Biol. 2020 May;27(5):472-479. doi: 10.1038/s41594-020-0410-z. Epub 2020 May 11.
Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor and regulate various physiological responses. Photoactivated CRYs undergo oligomerization, which increases the binding affinity to downstream signaling partners. Despite decades of research on the activation of CRYs, little is known about how they are inactivated. Binding of blue-light inhibitors of cryptochromes (BICs) to CRY2 suppresses its photoactivation, but the underlying mechanism remains unknown. Here, we report crystal structures of CRY2N (CRY2 PHR domain) and the BIC2-CRY2N complex with resolutions of 2.7 and 2.5 Å, respectively. In the BIC2-CRY2N complex, BIC2 exhibits an extremely extended structure that sinuously winds around CRY2N. In this way, BIC2 not only restrains the transfer of electrons and protons from CRY2 to FAD during photoreduction but also interacts with the CRY2 oligomer to return it to the monomer form. Uncovering the mechanism of CRY2 inactivation lays a solid foundation for the investigation of cryptochrome protein function.
隐花色素（CRYs）是植物中的蓝光受体，其辅因子为 FAD，并调节各种生理反应。光激活的 CRYs 发生寡聚化，从而增加与下游信号伴侣的结合亲和力。尽管对 CRYs 的激活进行了数十年的研究，但对于它们如何失活知之甚少。隐花色素蓝光抑制剂（BICs）与 CRY2 的结合抑制了其光激活，但潜在的机制尚不清楚。在这里，我们报告了 CRY2N（CRY2 PHR 结构域）和 BIC2-CRY2N 复合物的晶体结构，分辨率分别为 2.7 和 2.5 Å。在 BIC2-CRY2N 复合物中，BIC2 呈现出极其伸展的结构，蜿蜒地缠绕在 CRY2N 周围。通过这种方式，BIC2 不仅在光还原过程中抑制了电子和质子从 CRY2 向 FAD 的转移，而且还与 CRY2 寡聚体相互作用，使其恢复为单体形式。揭示 CRY2 失活的机制为研究隐花色素蛋白功能奠定了坚实的基础。
